The Emory Alzheimer's Disease Research Center (ADRC) Neuropathology Core (NP Core) supports the ADRC by providing comprehensive neuropathological assessment of patients and control subjects followed by the Clinical Core, by banking and distributing brain and spinal cord tissues for research studies, and by providing expert consultation to investigators regarding case selection and experimental design as they relate to the use of human tissues. During this funding period, the NP Core performed brain autopsies on 59 UDS subjects followed by the Clinical Core, and 6 MDS autopsies, and distributed >2200 tissue samples to 74 investigators leading to >180 peer-reviewed publications, chapters, and abstracts using Core resources. Our well-characterized tissue resources enables highly innovative research projects, such as Project 2 which uses unique proteomics methods to investigate novel targets for neurodegenerative disease, and Project 3 that is investigating differences in A? species that may explain disease variability. In this application, we will focus on elderly controls and patients with MCI, AD in order to facilitate research into the mechanisms of onset and progression of AD and related neurodegenerative diseases. To further contribute to innovative research in AD and related dementias, the NP Core is leveraging the amyotrophic lateral sclerosis (ALS) expertise of the NP Core leader, who provides new perspectives and resources for the pursuit of pathogenic mechanisms underlying clinically distinct, but pathologically similar diseases, some of which may coexist with AD. Together with the other ADRC Cores, the NP Core will educate students, residents, fellows, and investigators on neurodegenerative disease neuropathology and techniques used to evaluate neuropathological features in human brains and animal models of disease.